High Titer of Autoantibodies to GAD Identifies a Specific Phenotype of Adult-Onset Autoimmune Diabetes

  1. Raffaella Buzzetti, MD1,
  2. Sergio Di Pietro, MD2,
  3. Andrea Giaccari, MD3,
  4. Antonio Petrone, PHD1,
  5. Mattia Locatelli, MD4,
  6. Concetta Suraci, MD5,
  7. Marco Capizzi, MD1,
  8. Maria Luisa Arpi, MD6,
  9. Elena Bazzigaluppi, PHD7,
  10. Francesco Dotta, MD8,
  11. Emanuele Bosi, MD7 and
  12. for the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study Group*
  1. 1Department of Clinical Sciences, “La Sapienza” University, Rome, Italy
  2. 2Diabetes Unit Instituto Nazionale Riposo e Cura Anziani (INRCA), Rome, Italy
  3. 3Endocrinology, Catholic University, Rome, Italy
  4. 4Bambino Gesù Hospital, Rome, Italy
  5. 5Sandro Pertini Hospital, Rome, Italy
  6. 6Endocrinology, Garibaldi di Nesima Hospital, Catania University, Catania, Italy
  7. 7General Medicine, Diabetes and Endocrinology, San Raffaele Vita-Salute University, Milan, Italy
  8. 8Department of Internal Medicine, Siena University, Siena, Italy
  1. Address correspondence and reprint requests to Prof. Raffaella Buzzetti, MD, Azienda Policlinico Umberto I, Viale del Policlinico 155, 00161 Roma, Italy. E-mail: raffaella.buzzetti{at}uniroma1.it

Abstract

OBJECTIVE—The aim of the present study was to define heterogeneity of adult-onset autoimmune diabetes based on characterization of GAD antibodies (GADAs).

RESEARCH DESIGN AND METHODS—Patients enrolled in a nationwide survey, the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study, have been screened for GADAs and IA-2 antibodies (IA-2As) and further characterized for GADA titer, antibodies to thyroid peroxidase (TPO), and HLA DRB1-DQB1 polymorphisms.

RESULTS—Of 4,250 consecutive type 2 diabetic patients, 4.5% had either GADAs and/or IA-2As. Patients with autoimmune diabetes showed a clinical phenotype significantly different from that of type 2 diabetes, including higher fasting glucose and A1C, lower BMI and uric acid, lower prevalence of metabolic syndrome and its components, and higher frequency of TPO antibodies. More interestingly, analysis of GADA titers showed a bimodal distribution that identified two subgroups of patients with high (>32 GADA arbitrary units) and low (≤32 GADA arbitrary units) GADA titers. Compared with those with low GADA titers, patients with high GADA titers had more prominent traits of insulin deficiency and a profile of more severe autoimmunity resulting in higher A1C, lower BMI, a lower prevalence of metabolic syndrome and its components (P < 0.02 for all), a higher prevalence of IA-2As, TPO antibodies (P < 0.003 for both), and DRB1*03-DQB1*0201 (50 vs. 26.8%, P = 0.001), and a decreasing frequency of DQB1*0602 and DRB1*0403 (from type 2 to low and to high GADA titer autoimmune diabetes; P < 0.001 for trend for both comparisons).

CONCLUSIONS—GADA titers identify two subgroups of patients with adult-onset autoimmune diabetes having distinct clinical, autoimmune, and genetic features.

Footnotes

  • This article is dedicated to the memory of Professor Umberto Di Mario, who greatly contributed to the design and implementation of the study.

  • *

    ↵* Members of the Non Insulin Requiring Autoimmune Diabetes Study Group are listed in the appendix.

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted December 29, 2006.
    • Received August 10, 2006.
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  1. doi: 10.2337/dc06-1696 Diabetes Care April 2007 vol. 30 no. 4 932-938
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